FPI-2265 (225Ac-PSMA-I&T) for Patients with PSMA-Positive Metastatic Castration-Resistant Prostate Cancer (mCRPC)
- Conditions
- Metastatic Castration-resistant Prostate Cancer
- Interventions
- Drug: FPI-2265
- Registration Number
- NCT06402331
- Lead Sponsor
- Fusion Pharmaceuticals Inc.
- Brief Summary
This is an open-label, randomized, multicenter study of FPI-2265 (225Ac-PSMA-I\&T). The dose optimization Phase 2 part will be investigating the safety, tolerability, and anti-tumor activity of novel dosing regimens of FPI-2265 in participants with PSMA-positive mCRPC who have been previously treated with 177Lu-PSMA-617 or another 177Lu-PSMA radioligand therapy (RLT).
- Detailed Description
The purpose of the dose optimization segment (Phase 2) is to determine the recommended FPI-2265 dose and regimen. Conclusions from Phase 2 will be based on safety, tolerability, and anti-tumor activity.
Participants with PSMA positive scans will be randomized (1:1:1) to one of three different dosing arms:
Arm 1: Will consist of nine doses of FPI-2265, administered every four weeks at 50 kBq/kg.
Arm 2: Will consist of six doses of FPI-2265, administered every six weeks at 75 kBq/kg.
Arm 3: Will consist of four doses of FPI-2265, administered every eight weeks at 100 kBq/kg.
Participants will be monitored and assessed for efficacy response, disease progression and adverse events.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- Male
- Target Recruitment
- 60
- Ability to understand and sign an approved informed consent form (ICF) and comply with all protocol requirements.
- Phase 2: Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1
- Diagnosis of adenocarcinoma of prostate proven by histopathology.
- Must have had prior orchiectomy and/or ongoing androgen-deprivation therapy and a castrate level of serum/plasma testosterone
- Progressive mCRPC.
- Must have been previously treated with lutetium-PSMA therapy (lutetium-177 vipivotide tetraxetan or other lutetium-177-PSMA RLT). Treatment must have been completed >6 weeks prior to the first dose of study drug.
- Participants with known BRCA mutations should have received FDA-approved therapies such as PARP inhibitors, per Investigator discretion.
- Positive PSMA PET/CT scan
- Adequate organ function
- For participants who have partners of childbearing potential: Partner and/or participant must not be planning to conceive and must use a method of birth control with adequate barrier protection deemed acceptable by the Principal Investigator during the study treatment and for six months after last study drug administration.
Key
- Participants who received more than two prior lines of cytotoxic chemotherapy for CRPC.
- Phase 2: participants who progress within two cycles of prior treatment with 177Lu-PSMA therapy
- All prior treatment-related adverse events must have resolved to Grade ≤1 (CTCAE v5.0). Alopecia and stable persistent Grade 2 peripheral neuropathy may be allowed at the discretion of the Investigator.
- Participants with known, unresolved, urinary tract obstruction are excluded.
- Administration of any systemic cytotoxic or investigational therapy ≤30 days of the first dose of study treatment or five half-lives, whichever is shorter. Completion of large-field external beam radiotherapy ≤four weeks of the first dose of study treatment.
- Participants with a history of central nervous system (CNS) metastases are excluded except those who have received therapy
- Participants with any liver metastases will be excluded from the Phase 2 segment of the study.
- Participants with skeletal metastases presented as a superscan on a ⁹⁹ᵐTc bone scan.
- Previous or concurrent cancer that is distinct from the cancer under investigation in primary site or histology, except treated cutaneous basal cell carcinoma or squamous cell carcinoma and superficial bladder tumors. Any cancer curatively treated >two years prior to the first dose of treatment is permitted.
- Concurrent serious (as determined by the investigator) medical conditions
- Major surgery ≤30 days prior to the first dose of study treatment.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description FPI-2265 50 kBq/kg FPI-2265 Arm 1: FPI-2265 administered by IV injection every four weeks; up to 9 doses. FPI-2265 100 kBq/kg FPI-2265 Arm 3: FPI-2265 administered by IV injection every eight weeks; up to 4 doses. FPI-2265 75 kBq/kg FPI-2265 Arm 2: FPI-2265 administered by IV injection every six weeks; up to 6 doses.
- Primary Outcome Measures
Name Time Method Frequency, duration, and severity of treatment-emergent adverse events (TEAEs) From first dose until end of long-term follow-up, 5 years from the last administered dose of FPI-2265. Frequencies and percentages of participants with TEAEs will be summarized. Analysis will also be completed regarding duration of TEAEs and their severity.
Frequency and proportion of participants with PSA50 response From first dose until 12 weeks after the first administered dose of FPI-2265. PSA50 response is defined as a decline in PSA levels by at least 50% and is used to evaluate anti-tumor activity.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (13)
Hoag Health Center Irvine
🇺🇸Irvine, California, United States
VA Greater Los Angeles Healthcare System
🇺🇸Los Angeles, California, United States
Biogenix Molecular, LLC
🇺🇸Miami, Florida, United States
University of Iowa Hospitals and Clinics
🇺🇸Iowa City, Iowa, United States
United Theranostics
🇺🇸Glen Burnie, Maryland, United States
BAMF Health
🇺🇸Grand Rapids, Michigan, United States
SSM Health Saint Louis University Hospital
🇺🇸Saint Louis, Missouri, United States
XCancer
🇺🇸Omaha, Nebraska, United States
New Mexico Oncology Hematology Consultants Ltd.
🇺🇸Albuquerque, New Mexico, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone
🇺🇸New York, New York, United States
Memorial Sloan Kettering Cancer Center - NYC
🇺🇸New York, New York, United States
The University of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
U.T. MD Anderson Cancer Center
🇺🇸Houston, Texas, United States